1,4-Dioxane → rac-[(1R,2S,3R,4S)-3-({5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-yl}amino)bicyclo[2.2.1]hept-2-yl]methanol

HRID 38781Notes

Reaction equation

HRID 38781 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]([N:14]2[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1.[O:22]1[CH2:27][CH2:26]OCC1.C([N:31]([CH2:35][CH3:36])C(C)C)(C)C>O>[O:20]=[S:17]1(=[O:21])[CH2:18][CH2:19][N:14]([C:12]([C:5]2[C:6]([C:8]([F:11])([F:10])[F:9])=[N:7][C:2]([NH:31][C@@H:35]3[C@@H:36]4[CH2:4][C@@H:5]([CH2:6][CH2:8]4)[C@@H:26]3[CH2:27][OH:22])=[N:3][CH:4]=2)=[O:13])[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 581689914-{[2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide

Product 1

HCID 66720222rac-[(1R,2S,3R,4S)-3-({5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-yl}amino)bicyclo[2.2.1]hept-2-yl]methanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholin-1,1-dioxide (100 mg), 3-exo-hydroxymethylbicyclo[2.2.1]heptyl-2-exo-amine hydrochloride (129 mg), and 1,4-dioxane (3 mL) was added N,N-diisopropyl ethylamine (0.20 mL) at room temperature, and the mixture was stirred at 80° C. for 2 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to obtain rac-[(1R,2S,3R,4S)-3-({5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-yl}amino)bicyclo[2.2.1]hept-2-yl]methanol (72 mg) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-eaee6ecfb9a640bcb15d47a5c9aa967b
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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